Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV from the Canadian cohort of the observational BICSTaR study.

The BICSTaR (BICtegravir Single Tablet Regimen) study is investigating the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (HIV) treated in routine clinical practice. BICSTaR is an ongoing, prospective, observational cohort study across 14 countries. Treatment-naïve (TN) and treatment-experienced (TE) people with HIV (≥18 years of age) are being followed for 24 months. We present an analysis of the primary endpoint (HIV-1 RNA < 50 copies/mL; missing-equals-excluded [M = E]) at month 12 in the BICSTaR Canada cohort, including secondary (CD4 count, CD4/CD8 ratio, safety/tolerability) and exploratory (persistence, treatment satisfaction) endpoints. In total, 201 participants were enrolled in the BICSTaR Canada cohort. The analysis population included 170 participants (TN, n = 10; TE, n = 160), with data collected between November 2018 and September 2020. Of the participants, 88% were male, 72% were White, and 90% had ≥ 1 comorbid condition(s). Median (quartile [Q]1-Q3) age was 50 (39-58) years and baseline CD4 count was 391.5 (109.0-581.0) cells/µL in TN participants and 586.0 (400.0-747.0) cells/µL in TE participants. After 12 months of B/F/TAF treatment, HIV-1 RNA was < 50 copies/mL in 100% (9/9) of TN-active participants and 97% (140/145) of TE-active participants (M = E analysis). Median (Q1-Q3) CD4 cell count increased by +195 (125-307) cells/µL in TN participants and by + 30 (-50 to 123) cells/µL in TE participants. Persistence on B/F/TAF was high through month 12 with 10% (1/10) of TN and 7 % (11/160) of TE participants discontinuing B/F/TAF within 12 months of initiation of treatment. No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 7% (12/169) of participants, leading to B/F/TAF discontinuation in 4 of 169 participants. Improvements in treatment satisfaction were observed in TE participants. B/F/TAF demonstrated high levels of effectiveness, persistence, and treatment satisfaction, and was well tolerated through month 12 in people with HIV treated in routine clinical practice in Canada.

Clinical benefits of novel non-nucleoside reverse transcriptase inhibitors: A prospective cohort study.

INTRODUCTION: The efficacy and safety of ainuovirine+lamivudine+tenofovir (ANV+3TC+TDF) and efavirenz+lamivudine+tenofovir (EFV+3TC+TDF) have been confirmed in previous clinical trials; however, there are no related studies on patient-reported outcomes. This study aimed to evaluate the effectiveness and safety of these 2 antiretroviral therapy regimens and to understand the patient's symptom experience and subjective experience of sleep quality through patient-reported outcomes. METHODS: This is a single-center prospective cohort study with 243 patients evaluated from October 1, 2021 to June 30, 2022. Virological effectiveness and patient-reported outcomes results were analyzed. The primary endpoint was the proportion of HIV viral load <50 copies/mL (virological suppression rate) at 48 weeks and the changes in the HIV symptom index and Pittsburgh sleep quality index. RESULTS: The virological suppression rates in the ANV+3TC+TDF and EFV+3TC+TDF groups were 83.6% (102/122) and 87.6% (106/121), respectively, at 48 weeks. In the ANV+3TC+TDF group, the scores of HIV symptom index and pittsburgh sleep quality index in the 48th week were lower than the baseline level (p < 0.05). Logistic regression results showed that the baseline regimen EFV+3TC+TDF was a risk factor for dizziness/lightheadedness (odds ratio = 3.153, 95% confidence interval: 1.473-6.748, p = 0.003), sadness/depression odds ratio = 2.404, 95% confidence interval:1.188-4.871, p = 0.015), and difficulty sleeping (odds ratio = 2.802, 95% confidence interval: 1.437-5.463, p = 0.002) at 48 weeks. CONCLUSIONS: Both regimens showed good virological effectiveness; however, compared with ANV+3TC+TDF, the EFV+3TC+TDF regimen reduced the prevalence of HIV-related symptoms.

Treatment outcomes amongst older people with HIV infection receiving antiretroviral therapy.

OBJECTIVES: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH. METHODS: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test. RESULTS: Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction. CONCLUSION: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV.

Effects of statins beyond lipid-lowering agents in ART-treated HIV infection.

Antiretroviral therapies (ART) have reduced human immunodeficiency virus (HIV) infection-associated morbidity and mortality improving the life of people with HIV (PWH). However, ART lead to residual HIV production, which in conjunction with microbial translocation and immune dysfunction contributes to chronic inflammation and immune activation. PWH on ART remain at an increased risk for cardiovascular diseases (CVDs) including myocardial infarction and stroke; which in part is explained by chronic inflammation and immune activation. Lifestyle factors and certain ART are associated with dyslipidemia characterized by an increase of low-density lipoprotein (LDL), which further contributes in the increased risk for CVDs. Lipid-lowering agents like statins are emerging as immune modulators in decreasing inflammation in a variety of conditions including HIV. The international randomized clinical trial REPRIEVE has shed light on the reduction of CVDs with statin therapy among PWH. Such reports indicate a more than expected benefit of statins beyond their lipid-lowering effects. Bempedoic acid, a first-in-class non-statin LDL-lowering drug with immune modulatory effects, may further aid PWH in combination with statins. Herein, we critically reviewed studies aimed at lipid-lowering and immune-modulating roles of statins that may benefit aging PWH.

Prevalence of overweight and obesity among adolescents living with HIV after dolutegravir - based antiretroviral therapy start in Kampala, Uganda.

BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy (ART) is currently the preferred first-line treatment for persons living with HIV (PLHIV) including children and adolescents in many low- and middle-income countries including Uganda. However, there are concerns about excessive weight gain associated with DTG especially in adults. There remains paucity of current information on weight-related outcomes among adolescents on DTG. We determined the prevalence of excessive weight gain and associated factors among adolescents living with HIV (ALHIV) receiving DTG-based ART in Kampala, Uganda. METHODS: Cross-sectional study involving ALHIV aged 10-19 years on DTG-based ART for at least one year were recruited from public health facilities in Kampala between February and May 2022. Excessive weight gain was defined as becoming overweight or obese per body mass index (BMI) norms while on DTG-based ART for at least one year. Demographic, clinical and laboratory data were collected using interviewer-administered questionnaires and data extracted from medical records. At enrolment, blood pressure and anthropometry were measured and blood was drawn for blood glucose and lipid profile. Data was summarised using descriptive statistics and logistic regression was performed to determine the associated factors. RESULTS: We enrolled 165 ALHIV with a median age of 14 years (IQR 12-16). Eighty (48.5%) were female. The median duration on ART and DTG was 8 years (IQR 7-11) and 2 years (IQR 1-3) respectively. At DTG initiation, the majority of participants (152/165, 92.1%) were ART-experienced, and had normal BMI (160/165, 97%). Overall, 12/165 (7.3%) adolescents (95% CI: 4.2-12.4) had excessive weight gain. No factors were significantly associated with excessive weight gain after DTG start in ALHIV. However, all ALHIV with excessive weight gain were females. CONCLUSION: Our study found a prevalence of 7.3% of overweight and obesity in ALHIV after initiating DTG. We did not find any factor significantly associated with excessive weight gain in ALHIV on DTG. Nonetheless, we recommend ongoing routine monitoring of anthropometry and metabolic markers in ALHIV as DTG use increases globally, to determine the exact magnitude of excessive weight gain and to identify those at risk of becoming overweight or obese while taking the medication.

Renal Adverse Effects of Tenofovir Containing Regimens in HIV-Infected Children and Adolescents in North India.

OBJECTIVE: To study the prevalence of abnormal renal functions among children living with HIV (CLHIV) receiving tenofovir disoproxil fumarate (TDF) containing antiretroviral therapy (ART). METHODS: A prospective, observational study was conducted among CLHIV aged 10 years to 21 years attending the pediatric HIV clinic. We included CLHIV weighing ≥ 30 kg who had been receiving TDF-containing regimens for at least 6 months, with estimated glomerular filtration rate (eGFR) > 60 ml/min/m2 at enrolment and for whom baseline laboratory parameters were available before starting ART. Clinical and laboratory parameters like serum creatinine, serum phosphate, urinary protein and glucose estimation, CD4 count and viral load were noted from records. The mean change in serum creatinine, estimated glomerular filtration rate (eGFR), creatinine clearance, serum phosphate, and presence of urinary glucose and protein by dipstick were assessed at 3- and 12-months follow-up. RESULTS: We enrolled 70 patients with mean (SD) age 14.99 (2.45) years who had been receiving TDF-based ART for a mean (SD) duration of 14.60 (12.80) months. At 3-months and 12-months follow-up, 32.85% and 41.42% patients, respectively, had eGFR below 90 mL/min/1.73m2, while 4.2% and 2.8% patients, respectively, had eGFR between 50-60 mL/min/1.73m2. One patient had creatinine clearance below 50 mL/min/1.73m2. Four patients had hypophosphatemia at the first and last follow-up respectively, and five patients had proteinuria. There was no statistically significant change in CD4 counts, serum potassium, or serum uric acid during study duration. CONCLUSION: TDF-containing ART regimen is associated with decreased eGFR, creatinine clearance and proteinuria.

Challenges, risks, and opportunities of antiretroviral drugs in women of reproductive potential.

INTRODUCTION: The HIV/AIDS epidemic has been one of the greatest challenges in global health, significantly affecting women of reproductive potential. Considerable advances in antiretroviral therapy for women living with HIV have contributed to improvements in quality of life, better reproductive and birth outcomes, and a reduced risk of perinatal transmission. AREAS COVERED: Despite the progress made, persistent challenges in access and adherence to antiretroviral drugs may limit their benefits for some women. More pharmacokinetic and safety studies in pregnant and lactating women are urgently needed, as are prospective surveillance systems to evaluate associations between fetal and infant antiretroviral exposures, drug-drug interactions, and pregnancy outcomes. EXPERT OPINION: Multipurpose technologies, such as combined HIV and other STI or unintended pregnancy prevention, and innovative delivery methods, such as the development of long-acting antiretrovirals, have the potential to reduce adherence challenges and enhance quality of life for women with HIV. Parallel advances in drug safety testing and surveillance are needed to ensure the health and safety of women with or at risk for HIV and children at risk for perinatal transmission.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies.

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

HIV-TB Coinfection: Current Therapeutic Approaches and Drug Interactions.

The co-occurrence of human immunodeficiency virus (HIV) and tuberculosis (TB) infection poses a significant global health challenge. Treatment of HIV and TB co-infection often necessitates combination therapy involving antiretroviral therapy (ART) for HIV and anti-TB medications, which introduces the potential for drug-drug interactions (DDIs). These interactions can significantly impact treatment outcomes, the efficacy of treatment, safety, and overall patient well-being. This review aims to provide a comprehensive analysis of the DDIs between anti-HIV and anti-TB drugs as well as potential adverse effects resulting from the concomitant use of these medications. Furthermore, such findings may be used to develop personalized therapeutic strategies, dose adjustments, or alternative drug choices to minimize the risk of adverse outcomes and ensure the effective management of HIV and TB co-infection.

Safety of teropavimab and zinlirvimab with lenacapavir once every 6 months for HIV treatment: a phase 1b, randomised, proof-of-concept study.

BACKGROUND: Long-acting treatment for HIV has potential to improve adherence, provide durable viral suppression, and have long-term individual and public health benefits. We evaluated treatment with two antibodies that broadly and potently neutralise HIV (broadly neutralising antibodies; bNAbs), combined with lenacapavir, a long-acting capsid inhibitor, as a long-acting regimen. METHODS: This ongoing, randomised, blind, phase 1b proof-of-concept study conducted at 11 HIV treatment centres in the USA included adults with a plasma HIV-1 RNA concentration below 50 copies per mL who had at least 18 months on oral antiretroviral therapy (ART), CD4 counts of at least 500 cells per µL, and protocol-defined susceptibility to bNAbs teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS). Participants stopped oral ART and were randomly assigned (1:1) to one dose of 927 mg subcutaneous lenacapavir plus an oral loading dose, 30 mg/kg intravenous teropavimab, and 10 mg/kg or 30 mg/kg intravenous zinlirvimab on day 1. Investigational site personnel and participants were masked to treatment assignment throughout the randomised period. The primary endpoint was incidence of serious adverse events until week 26 in all randomly assigned participants who received one dose or more of any study drug. This study is registered with ClinicalTrials.gov, NCT04811040. FINDINGS: Between June 29 and Dec 8, 2021, 21 participants were randomly assigned, ten in each group received the complete study regimen and one withdrew before completing the regimen on day 1. 18 (86%) of 21 participants were male; participants ranged in age from 25 years to 61 years and had a median CD4 cell count of 909 (IQR 687-1270) cells per µL at study entry. No serious adverse events occurred. Two grade 3 adverse events occurred (lenacapavir injection-site erythaema and injection-site cellulitis), which had both resolved. The most common adverse events were symptoms of injection-site reactions, reported in 17 (85%) of 20 participants who received subcutaneous lenacapavir; 12 (60%) of 20 were grade 1. One (10%; 95% CI 0-45) participant had viral rebound (confirmed HIV-1 RNA concentration of ≥50 copies per mL) in the zinlirvimab 10 mg/kg group, which was resuppressed on ART, and one participant in the zinlirvimab 30 mg/kg group withdrew at week 12 with HIV RNA <50 copies per mL. INTERPRETATION: Lenacapavir with teropavimab and zinlirvimab 10 mg/kg or 30 mg/kg was generally well tolerated with no serious adverse events. HIV-1 suppression for at least 26 weeks is feasible with this regimen at either zinlirvimab dose in selected people with HIV-1. FUNDING: Gilead Sciences.

Body weight and blood pressure changes on dolutegravir-, efavirenz- or atazanavir-based antiretroviral therapy in Zimbabwe: a longitudinal study.

INTRODUCTION: Dolutegravir (DTG) is widely used for antiretroviral therapy (ART). We compared weight and blood pressure trends and examined the association between high blood pressure and weight gain among people living with HIV (PLHIV) switching to or starting DTG-based, efavirenz (EFV)-based and ritonavir-boosted atazanavir (ATV/r)-based ART in Zimbabwe. METHODS: PLHIV aged 18 years or older who started or switched to DTG, EFV or ATV/r-based ART between January 2004 and June 2022 at Newlands Clinic in Harare, Zimbabwe, were eligible. Weight was measured at all visits (Seca floor scales); blood pressure only at clinician-led visits (Omron M2 sphygmomanometer). We used Bayesian additive models to estimate trends in weight gain and the proportion with high blood pressure (systolic >140 mmHg or diastolic >90 mmHg) in the first 2 years after starting or switching the regimen. Finally, we examined whether trends in the proportion with high blood pressure were related to weight change. RESULTS: We analysed 99,969 weight and 35,449 blood pressure records from 9487 adults (DTG: 4593; EFV: 3599; ATV/r: 1295). At 24 months after starting or switching to DTG, estimated median weight gains were 4.54 kg (90% credibility interval 3.88-5.28 kg) in women and 3.71 kg (3.07-4.45 kg) in men, around twice that observed for ATV/r and over four-times the gain observed for EFV. Prevalence of high blood pressure among PLHIV receiving DTG-based ART increased from around 5% at baseline to over 20% at 24 months, with no change in PLHIV receiving EFV- or ATV/r-based ART. High blood pressure in PLHIV switching to DTG was associated with weight gain, with stronger increases in the proportion with high blood pressure for larger weight gains. CONCLUSIONS: Among PLHIV starting ART or switching to a new regimen, DTG-based ART was associated with larger weight gains and a substantial increase in the prevalence of high blood pressure. Routine weight and blood pressure measurement and interventions to lower blood pressure could benefit PLHIV on DTG-based ART. Further studies are needed to elucidate the mechanisms and reversibility of these changes after discontinuation of DTG.

Mechanism of action, resistance, interaction, pharmacokinetics, pharmacodynamics, and safety of fostemsavir.

The Food and Drug Administration (FDA) has licensed many antiretroviral medications to treat human immunodeficiency virus type 1 (HIV-1), however, treatment options for people with multi-drug resistant HIV remain limited. Medication resistance, undesirable effects, prior tolerance, and previous interlacement incapacity to deliver new drug classes all lead to the requirement for new medication classes and drug combination therapy. Fostemsavir (FTR) is a new CD-4 attachment inhibitor medicine that was recently authorized by the United States FDA to treat HIV-1. In individuals with multidrug-resistant (MDR) HIV-1, FTR is well tolerated and virologically active. According to recent investigations, drug combination therapy can positively affect MDR-HIV. The mechanism of action, resistance, interaction, pharmacokinetics, pharmacodynamics, and safety of FTR has been highlighted in this review.

Bidirectional pharmacokinetics of doravirine, tenofovir, and feminizing hormones in transgender women (IDentify): A randomized crossover trial.

Transgender women may have concerns of drug interactions between feminizing hormone therapy (FHT) and antiretrovirals, leading to nonadherence. This randomized, three-period crossover, open-label, phase I trial assessed the effects of doravirine (DOR) and tenofovir disoproxil fumarate (TDF) on the pharmacokinetics (PKs) of estradiol, spironolactone, and total testosterone and vice versa in healthy transgender women. Volunteers were randomized 1:1 into two sequences containing three treatment groups (DOR, lamivudine [3TC], and TDF alone; estradiol, spironolactone, and placebo; and DOR/3TC/TDF, estradiol, and spironolactone). Eight subjects enrolled in the study and six had completed all study periods. The geometric mean ratios for DOR area under the concentration-time curve from zero to last measured concentration (AUC0-last ), maximum concentration (Cmax ), and concentration at 24 h (C24 ) were similar. However, tenofovir (TFV) AUC0-last , Cmax , and C24 moderately increased by 14%-38%. Last, estradiol AUC0-last , Cmax , and C24 were increased by 10%-13%. Whereas most 90% confidence intervals did not meet the bioequivalence bounds of 80%-125%, the point estimates fell within the intervals. Log-transformed DOR, TFV, and estradiol PK parameters computed with and without co-administration were not statistically different (p > 0.05). There were no serious adverse events. There is not a clinically significant impact of FHT on DOR/TFV PKs. Similarly, there is no observed impact on estradiol PKs and total testosterone following use of DOR/3TC/TDF.

Effects of Prolonged Administration of Tenofovir Disoproxil Fumarate-Containing Antiviral Regimen on Renal Function in Low-Risk of Kidney Injury HIV Patients.

This study intended to investigate the impact of long-term tenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)-infected patients with low-risk of kidney injury. The observational study involving 100 HIV-infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+ lamivudine+ efavirenz (TLE) for 3.19 years. Renal function, including estimated glomerular filtration rate (eGFR), blood and urine ß2 microglobulin, and other parameters, was assessed every 3 months over a period of 2.5 years. The eGFR showed a slight increasement from 116.0 at month 0 to 119.7 at month 30. Blood ß2 microglobulin increased from 2.02 mg/L at month 0 to 2.77 mg/L at month 30. Compared to month 0, the difference in blood ß2 microglobulin was statistically significant at month 6 and months 12-30 (P < .05). The incidence of proximal renal tubular dysfunction fluctuated from 2% at month 0 to 2.5% at month 30. The urine ß2 microglobulin fluctuated from 0.5 (0.3-1.1) to 0.8 (0.5-1.35) mg/L at months 18-30, which was higher than 0.41 (0.18-1.1) mg/L at month 0 (P < .05). The abnormal concentration proportion of urine ß2 microglobulin fluctuated from 72.7% to 81.3% at months 18-30, which was higher than the proportion of 57.0% at month 0. The abnormal proportion of blood ß2 microglobulin, urine ß2 microglobulin, and proximal renal tubular dysfunction were not correlated with eGFR (r1 = 0.119, r2 = -0.008, r3 = -0.165, P > .05). Long-term TDF antiviral regimen in low-risk of kidney injury HIV-infected patients may lead to damage in the proximal renal tubules and glomeruli. Blood and urine ß2 microglobulin levels may be helpful in screening for renal dysfunction.

DOLAMA 200: Effectiveness and Safety of a Dual Therapy with Dolutegravir Plus Lamivudine in Treatment-Experienced HIV-1 Infected Real World Participants in Spain.

The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles.

Switching to dolutegravir plus rilpivirine versus maintaining current antiretroviral therapy regimen in virologically suppressed people with HIV-1 and the Lys103Asn (K103N) mutation: 48-week results from a randomised, open-label pilot clinical trial.

BACKGROUND: The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens. METHODS: In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38. FINDINGS: Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups. INTERPRETATION: Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine. FUNDING: ViiV Healthcare.

Adverse drug reactions attributed to generic substitution of antiretroviral medications among HIV treatment and pre-exposure prophylaxis clients in British Columbia, Canada.

BACKGROUND: In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs. METHODS: Cohorts included DTP clients ≥19 years who received generic ARVs for HIV-Tx (abacavir-lamivudine, emtricitabine-tenofovir DF, efavirenz-emtricitabine-tenofovir DF, atazanavir or darunavir between 01 Jun 2017 and 30 Jun 2022) or PrEP (emtricitabine-tenofovir DF, 01 Apr 2018 to 30 Jun 2022). Demographic, ARV and ADR data were extracted from DTP databases and summarized by descriptive statistics. PSI incidence was calculated for each product during the year following brand-to-generic and generic-to-generic transitions (first-year-post-rollout), and compared between generic versions using generalized estimating equations. For context, incidence of any ARV product-related ADR was calculated in the same 1-year periods. RESULTS: During first-year-post-rollout periods, 5339 HIV-Tx (83% male, median age 52 years) and 8095 PrEP (99% male, median 33 years) clients received generic ARVs, and reported 78 and 23 generic PSIs, respectively. PSI incidence was <1% for most generic ARVs, with mild-moderate symptoms including gastrointestinal upset, headache, dizziness, fatigue/malaise and skin rash. In HIV-Tx clients, the efavirenz-containing product had higher PSI incidence than other ARVs (2.2%, p = .004), due to more neuropsychiatric adverse reactions. Any ADR incidence was stable across measurement periods, and generic PSIs represented less than one third of all product-related ADRs. CONCLUSIONS: Generic substitution of antiretrovirals for HIV-Tx and PrEP was well tolerated, with ≤2% incidence of mild-moderate PSI ADRs.

Acute facial neuralgia related to initiation of emtricitabine/tenofovir for HIV PrEP: a report of two cases in a PrEP demonstration trial.

BACKGROUND: Emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) fixed-dose combination (FTC/TDF) is generally well-tolerated, although treatment-related adverse events have been reported. METHODS: We report two cases of persons using FTC/TDF PrEP who had acute neuralgia in a Chinese PrEP demonstration trial. RESULTS: Neurological symptoms subsided upon treatment discontinuation. Symptoms were reported as similar to one case's previous experiences with dolutegravir (DTG)+FTC+tenofovir alafenamide (TAF) (for PEP), leading to permanent discontinuation of PrEP. CONCLUSION: Acute facial neuralgia appears to be a rare idiosyncratic adverse event to FTC/TDF.

Favorable Virological Outcome, Characteristics of Injection Site Reactions, Decrease in Renal Function Biomarkers in Asian People with HIV Receiving Long-Acting Cabotegravir Plus Rilpivirine.

Long-acting cabotegravir plus rilpivirine has revolutionized the concept of antiretroviral therapy, but as the causes of virological failure and satisfaction can depend on patient background, real-world data are needed. In this single-center study, we reviewed clinical records of people with HIV (PWH) who received injectable cabotegravir plus rilpivirine between June 2022 and January 2023. We assessed virological and safety outcomes, including injection site reactions (ISRs) and changes in serum creatinine and cystatin C. Seventy-four patients were included. There were no virological failures. Approximately 80% of individuals achieved HIV-RNA undetectable in all visits up to 14 months (median 13 months) after switching. Pain upon injection was significantly more common at the rilpivirine injection site, while delayed pain was significantly more common at the cabotegravir injection site. The serum creatinine (mean difference -0.12 mg/dL, p < .0001) and the cystatin C (mean difference -0.077 mg/dL, p < .0001) decreased significantly after switching, and in multivariable regression analysis, baseline characteristics did not affect the decrease in these renal function markers. Long-acting cabotegravir plus rilpivirine showed excellent antiviral efficacy and safety in PWH in Japan. ISRs were characterized differently at the cabotegravir and rilpivirine injection sites. Although cystatin C showed decrease after the regimen switch, further confirmation is needed whether cabotegravir plus rilpivirine can improve renal function.